Catalytic hydrogenation is one of the fundamental reactions in chemistry, and is used in a large number of chemical processes. It is now recognized that catalytic hydrogenations of carbon-carbon double bonds of alkenes, and carbon-heteroatom double bonds of ketones, aldehydes and imines are indispensable processes for the production of the wide range of alkanes, alcohols and amines, including chiral compounds, which are useful as valuable end products and precursors for the pharmaceutical, agrochemical, flavor, fragrance, material and fine chemical industries.
Amongst the several different kinds of processes known to achieve such transformations, two important types are: (a) transfer hydrogenation processes, in which hydrogen-donors such as secondary alcohols, and in particular isopropanol (iPrOH), and triethylammonium formate (HCOOH/NEt3) are used, and (b) hydrogenation processes, in which molecular hydrogen is used. Both hydrogen transfer and hydrogenation processes need a catalyst or catalytic system to activate the reducing agent, such as an alcohol, HCOOH/NEt3 or molecular hydrogen.
The catalytic hydrogenation processes developed by Noyori and coworkers (Ohkuma et al., J. Am. Chem. Soc., 1995, 107, 2675 and 10417) are very attractive, since the catalysts consist of air-stable ruthenium complexes of the type RuCl2(PR3)2(diamine) and RuCl2(diphosphine)(diamine) which are precursors for the generation of what appears to be some of the most active catalysts for the homogeneous and asymmetric hydrogenation of ketones and imines in the presence of a base and hydrogen gas. It has been proposed and subsequently mechanistically elucidated that the key molecular recognition feature of these catalysts is the presence of mutually cis N—H and Ru—H moieties of the catalytic dihydride species (RuH2(PR3)2(diamine) and RuH2(diphosphine)(diamine)) that electronically bind and activate the substrate and facilitate reduction.
Transfer hydrogenation, whereby a hydrogen donor solvent such as 2-propanol or HCOOH/NEt3 serves as the reducing agent, though currently not as highly developed as catalytic hydrogenation, is widely recognized as a potentially lucrative niche technology that is particularly significant and attractive whenever hydrogenation, for whatever reason, is not applicable or practical. Hence, transfer hydrogenation is complimentary to hydrogenation processes, especially for small to medium scale transformations. In most cases, 2-propanol is the conventional hydrogen donor solvent of choice because it is stable, non-toxic, has a moderate boiling point (82° C.), is readily available, inexpensive and environmentally friendly.
Amongst the potentially interesting transfer hydrogenation catalysts reported in the prior art to activate 2-propanol, there are ruthenium complexes with tetradentate diaminediphosphine ligands, (Gao et al. in Tianranqi Huagong, 1995, 20, 1 or CN 1047597 B) and the analogous ruthenium complexes with tetradentate diiminediphosphine ligands, (Xu et al. in Yingyong Huaxue 1997, 14, 58 or Gao et al. in Chirality, 2000, 12, 383). The reported processes, using these two types of complexes, relate to their use for the reduction of carbon-oxygen double bonds, such as those found in ketones and aldehydes.
Noyori and coworkers have also described an efficient catalyst system. generated from the complex Ru(η6-arene)(tosyldiamine)Cl for the asymmetric hydrogenation of ketones and imines by transferring hydrogen from triethylammonium formate (Noyori et al., Acc. Chem. Res. 1997, 30, 97-102). More recently, Blacker et al. demonstrated that cyclopentadienylrhodium and areneruthenium complexes in the presence of tosylated diamines and aminoalcohols are very efficient catalysts for the transfer hydrogenation of a wide range of ketones, imines and iminium salts under mild reaction conditions (A. J. Blacker et al., U.S. Pat. No. 6,372,931 B1, 2002; U.S. Pat. No. 6,509,467 B1, 2003).
There are some reports in the literature of the preparation of tridentate aminodiphosphine ligands and their transition metal complexes, including the use of some of these complexes for hydrogenation reactions, involving the use of hydrogen gas as the reducing agent (M. J. Burk et al., Tetrahedron: Asymmetry, 1991, 2, 569; M. J. Burk et al., U.S. Pat. No. 5,258,553, 1993; M. M. Taqui Khan et al., J. Mol. Catal., 1987, 42, 161; M. M. Taqui Khan et al., Polyhedron, 1987, 6, 1727). None of these reports describes processes in which such complexes are used for transfer hydrogenation processes, involving a hydrogen donor solvent as the reducing agent.